12-10415652-TTA-T

Variant names:

• chr12-10415652-TTA-T
• rs749992751
• ENST00000381903.2:c.728_729delTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007333.2(KLRC3):​c.728_729delTA​(p.Ile243LysfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,608,872 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (45 hom.)
• Consequence: KLRC3 NM_007333.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.490
• Publications: 0 publications found

Genes affected

KLRC3 (HGNC:6376): (killer cell lectin like receptor C3) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. KLRC3 is a member of the NKG2 group which are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The NKG2 gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000255641 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-10415652-TTA-T is Benign according to our data. Variant chr12-10415652-TTA-T is described in ClinVar as Benign. ClinVar VariationId is 776694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (2109/152282) while in subpopulation AFR AF = 0.0483 (2008/41548). AF 95% confidence interval is 0.0466. There are 40 homozygotes in GnomAd4. There are 962 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007333.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC3	NM_002261.3	MANE Select	c.678+50_678+51delTA		intron	N/A	NP_002252.2	Q07444-1
	KLRC3	NM_007333.2		c.728_729delTA	p.Ile243LysfsTer10	frameshift	Exon 6 of 6	NP_031359.2	Q07444-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC3	ENST00000381903.2	TSL:1	c.728_729delTA	p.Ile243LysfsTer10	frameshift	Exon 6 of 6	ENSP00000371328.2	Q07444-2
	KLRC3	ENST00000396439.7	TSL:5 MANE Select	c.678+50_678+51delTA		intron	N/A	ENSP00000379716.3	Q07444-1
	ENSG00000255641	ENST00000539033.1	TSL:1	c.678+50_678+51delTA		intron	N/A	ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2107 AN: 152164 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00368 AC: 905 AN: 245718 AF XY: 0.00265

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000629

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00135 AC: 1965 AN: 1456590 Hom.: 45 AF XY: 0.00115 AC XY: 830 AN XY: 724388

African (AFR) AF: 0.0503 AC: 1669 AN: 33150

American (AMR) AF: 0.00219 AC: 96 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.000118 AC: 10 AN: 85002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53254

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5736

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1109876

Other (OTH) AF: 0.00269 AC: 162 AN: 60182

GnomAD4 genome AF: 0.0138 AC: 2109 AN: 152282 Hom.: 40 Cov.: 32 AF XY: 0.0129 AC XY: 962 AN XY: 74466

African (AFR) AF: 0.0483 AC: 2008 AN: 41548

American (AMR) AF: 0.00477 AC: 73 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68010

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00132 Hom.: 0

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=187/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs749992751; hg19: chr12-10568251;